Structural basis for RNA trimming by RNase T in stable RNA 3′-end maturation
Structural basis for RNA trimming by RNase T in stable RNA 3′-end maturation
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DOI：
10.1038/nchembio.524
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发表时间：
2011-04-01
影响因子：
14.8
通讯作者：
Yuan, Hanna S.
中科院分区：
文献类型：
--
作者：
Hsiao, Yu-Yuan;Yang, Che-Chuan;Yuan, Hanna S.
RNA的成熟依赖于各种核酸外切酶来连续地从核酸的5‘或3’端去除核苷酸。然而，对于核酸外切酶底物和切割偏好的分子基础却知之甚少。我们对RNaseT-DNA复合体的生化和结构分析表明，RNaseT二聚体具有理想的结构，可以将双链与短的3‘端结合，产生带有2-核苷酸(NT)或1-NT 3’端的双链的消化产物，这取决于双链中最后一个碱基对的组成。核糖核酸酶T中的‘C-过滤器’通过诱导活性部位的破坏性构象变化，筛选出含有3‘-末端胞嘧啶的核酸进行水解。我们的结果揭示了RNaseT在稳定RNA成熟过程中进行最终修剪的一般原理和作用机制，为理解其他DEDD家族核酸外切酶奠定了基础。
RNA maturation relies on various exonucleases to remove nucleotides successively from the 5' or 3' end of nucleic acids. However, little is known regarding the molecular basis for substrate and cleavage preference of exonucleases. Our biochemical and structural analyses on RNase T-DNA complexes show that the RNase T dimer has an ideal architecture for binding a duplex with a short 3' overhang to produce a digestion product of a duplex with a 2-nucleotide (nt) or 1-nt 3' overhang, depending on the composition of the last base pair in the duplex. A 'C-filter' in RNase T screens out the nucleic acids with 3'-terminal cytosines for hydrolysis by inducing a disruptive conformational change at the active site. Our results reveal the general principles and the working mechanism for the final trimming step made by RNase T in the maturation of stable RNA and pave the way for the understanding of other DEDD family exonucleases.